Process for preparing carbanilates

ABSTRACT

There is disclosed herein a process for the preparation of aromatic amines and carbamates by reacting certain carbocyclic and heterocyclic aromatic compounds, ring-substituted with at least one displaceable substituent with alkali metal cyanates and water or an alkanol in the presence of a high dielectric-aprotic solvent.

I United States Patent 1 1 111i 3,882,165

Pews et a1. I May 6, 1975 1 1 PROCESS FOR PREPARING [56] ReferencesCited CARBANILATES UNITED STATES PATENTS [75] Inventors; Richard GarthPews; Lennon H. 3.584.028 6/197] Argahright et al H 260/453 McKendry,both Of Midland, Mich 3,773.695 11/1973 Argahright et lll,., 260/248 NSRalph M. Rodia, Salem. Oreg.

(73] Assignee: The Dow Chemical Company,

Midland. Mich, Primary E.i'aminerAlan L, Rutman Attorney, Agent, orFirm-Gary D. Street [22] Filed: Nov. 1, 1973 2| Appl. No: 411,943

Related U.S. Application Data 1 1 ABSTRACT [60} Division of Ser No.285.503. Aug 31. I972. Pill, No, There is disclosed herein a process forthc prepuratiun 3,804.844. and a continuution-in-part of Ser. Nu ofaromatic amines and carbamatcs by reacting cer- 94.622. Dec. 2. 1970,lain carbocyclic and hcterocyclic aromatic cunt puunds. ring-substitutedwith at least one displaceahle [52] U.S. Cl ..260/47l C;260/248 NS;substitucnt with alkali metal cyanatcs and water or an 260/294.8 F;260/295 CA; 260/296 R: ulkanol in the presence of a highdiclcclric-aprotic sul- 260/578 vent. [51 Int. Cl. C07c 125/06 8 Cl N Dv [58] Field of Search... 260/2948 F. 295 CA, 2% R, 0

260/248 NS, 471 C l PROCESS FOR PREPARING (.ARIIANIIATES CROSS-REFERENCETO REIA'I'EI) APPLICATION This is a division of application Ser. No.3\'5.5U3. filed Aug. 31. I972. now US. Pat. No. 3.804.844. The presentapplication is a continuation in-part of our copending application. Ser.No. 94.622. tiled Dec. 2.

BACKGROUND OF THE INVENTION The present invention pertains to a newmethod for preparing aromatic amines and carbamates by reacting certainring substituted aromatic carboeyclic and beterocyclic compounds withalkali metal cyanatcs and water or an alkanol.

Various methods for preparing certain organic isocyanate-basedderivatives are disclosed in the art. It is generally known that certainorganic isocyanate intermediates are prepared by the reaction ofphosgenc with amines. or by the rearrangement of appropriate acylaiides. The preparation of organic isocyanates by the reaction ofaralkyl and aralkenyl halides. such as benzyl chloride and xylylenedichloride. with alkali metal cyanates in the presence of quaternaryammonium halides or tertiary amines is also known. See U.S. Pat. Nos.2.866.802 and 2.866.803. The reaction of similar organic halides withalkali cyanates to form isocyanates is also known in the art. Generally,the reac tive halide is present on an aliphatic carbon atom having atleast one hydrogen atom on the halogensubstituted atom. See. forexample. U.S. Pat. Nos. 2.536.849; 2.886.8Ul; and 3.584.028.

It has now been discovered that aromatic ringsubstitutedisocyanate-bascd derivatives can be prepared from variousringsubstituted aromatic carbocyclic and heterocyclic compounds;furthermore. the process can be carried out without prior or separatereduction to a corresponding amine.

SUMMARY OF THE INVENTION According to the present invention. it has beendiscovered that carbocyclic and heterocyclic aromatic amines andcarbamates. hereinafter termed isocyanate-based compounds." can beprepared by reacting certain carbocyclic and heterocyclic aromaticcompounds. ring-substituted with at least one displaceable substituent.with alkali metal cyanates and water or an alkano] in the presence ofahigh dielectric-aprotic solvent. Other isocyanate-based compounds. suchas for example. aromatic isocyanurates. are prepared in similar methodswherein aromatic carbocyclic or heterocyclic compounds. ring-substitutedwith at least one displaceable substituent. are reacted with alkalimetal cyanates in the presence of a high dielectric-aprotic sol vent.

The process of the present invention is generally applicable tocarbocyclic or hetcrocyclic aromatic compounds (hcreinafter "aromaticcompounds") ringsuhstituted with at least one substitucnt subject tonucleophilic displacement by a cyanate ion nucleophile. Such aromaticcompounds can be ring-substituted with more than one identical ordifferent displaccable substituents which can be of the same or ofvarying degrees of nucleophilic reactivity with a cyanate ionnucleophile. Furthermore. the aromatic compounds can contain one or morenon-displaccable substituents. i.e.. not dis plaeeablc by a cyanate ionnucleophile. as long as at least one ring-substituted displaceablcsubstitucnt is present. Such isocyanate-based derivatives have estbalished utility in a variety of applications such as. for example.bonding agents. pesticides. additives or modifiers in polymers toincrease fire retardancy and water repellancy. and the like. Other useswill be evident to those skilled in the art.

DETAILED DESCRIPTION OF THE INVENTION Examples of specific aromaticcompounds which. when ring-substituted with at least one displace-ablesubstituent. are useful in the present process include. for example.bcm'enc. pyridine. pyrimidine. pyrazine. pyran. quinoxaline. indaxole.furan. pyrrole. thiophene. imidazole. oxazole. isoxazole and the like.Of these. benzene. pyridine. pyrimidine. pyrazine. pyran. quinoxaline.and indazole constitute a preferred class. A preferred sub-class ofcompounds within this invcntion are bcnlene. pyridine. pyrimidine andpyrazine. Within this preferred sub-class especially preferred arebenzene and pyridine. Substituents which are subject to nucleophilicdisplacement by a cyanate ion nuclcophili and which can bering-substituted on the above aromatic compounds include chloro. bromo.lluoro. iodo. N OSO R. SO R. or SR wherein each R independentlyrepresents hydrogen. phenyl or a loweralkyl radical of from I to about 4carbon atoms. inclusive.

The following definitions will aid in the understand ing of thedisclosed invention. The term aprotic sol vent means a solvent whichdoes not yield a proton to the solutcts) under reaction conditions. Forpurposes of this invention. high dielectric" refers to compounds havinga dielectric constant equal to or higher than diglyme. otherwise knownas diethylcneglycol dimethyl ether." The term loweralkyl" as used in thepresent specification and claims. means saturated. monovalent aliphaticradicals, including straight and branchedchain radicals of from one toabout 4 carbon atoms. as illustrated by. but not limited to. methyl.ethyl. propyl. isopropyl. butyl sec.-butyl. and the like.

The alkali metal cyanates which can be employed in the present inventioninclude those of lithium. sodium. potassium. and cesium; preferablysodium and potas sium cyanate are employed. Normally. it is advantageousto employ from about It) to about 50% equivalent excess of alkali metalcyanate.

The high dielectric-aprotic solvents useful in this invention includeacetonitrile. dimethylssulfoxide. dimethyl formamide. diglymc (otherwiseknown as diethyleneglycol dimethyl ether). monoglyme (otherwise known as1.2-dimethoxyethane acetone. methyl ethyl ketone. dioxanc.tetrahydrofuran. N- methylpyrrolidone. and the like. Of these solvents.acetonitrile and N-methylpyrrolidone are especially preferred.Representative alkanols suitable for use in the present invention arethose containing from I to about 4 carbon atoms. including methanol.ethanol. propanol. iso-propanol. butanol. and the like.

In carrying out the process of the present invention. the aromaticring-substituted compound and alkali metal cyanate contacted in thepresence of a high die Iectricaprotic solvent. Water or an alkanol isadded and the resulting reaction mixture is heated for a sufficientperiod of time to allow for substantial completion of the reaction. Theisocyanate-based compound obtained upon the addition of water alone isthe corresponding aromatic amine. whereas the aromatic carbamate isobtained upon the addition of an alkanol only. Mixtures of the amine andcarbamate compounds are obtained upon the addition of both water andalka nol. In each instance. the aromatic amine and carbamate productsare derived from a common isocyanate intermediate. in alternativeoperations. the water or alka nol can be added to the reaction mixturefollowing the initial heating of the aromatic compound and alkali metalcyanate reactant. Where it is desired to produce other isocyanatebasedcompounds. such as. for example. aromatic isocyanurates. the additionolwater or an alkanol is omitted.

The temperature at which the reaction is carried out is dependent uponthe raw material reactants and solvent employed. Generally. the reactiontemperature ranges from about 20 to about 200C.'. preferably. thereaction is carried out at the boiling temperature of the reactionmixture under reflux conditions. Similarly, the reaction time. whichranges from about I hour to 4 or days. varies inversely with thereaction temperature. Ambient pressures are adequate at the reactiontemperature employed when the volatility of the aromatic reactant.alcohol. and solvent permit; many reactions of the invention can becarried out at atmospheric pressure.

To further illustrate the process ofthe present invention. the followingexamples are provided. It should be understood that the details thereofare not to be regarded as limitations. as they may be varied as will beunderstood by one skilled in the art.

EXAMPLE 1 A reaction mixture consisting of 2.4-dinitrochlorobenzene(25.0 grams; 0.123 mole). potassium cyanate (12.0 grams; 0.184 mole].7.5 milliliters of methanol and 50 milliliters of acetonitrile washeated with agita' tion at the boiling point of the mixture under refluxconditions for a period of about 5 days. Following the reaction period.the reaction mixture was filtered while hot to remove solid byproductsand the filtrate was cooled to about l0C. The red precipitate formedupon cooling of the filtrate was removed by filtration and dissoh ed inchloroform to give a yellow solution containing a red solid. Thesolution was filtered and the filtrate concentrated to dryness byevaporation under reduced pressure. The residue thus obtained waspurified by exposure to column chromatography using chloroform as theeluent and activated alumina as an adsorbent. and by subsequentrecrystallization from carbon tetrachloride. As a result of theseoperations. the desired methyl 2.4dinitrocarbanilate product wasobtained as a crystalline solid melting at 127 to l27.5C

EXAMPLE 2 A reaction mixture consisting of 4-methylsult'onyl-2.3.5.o-tetrachloropyridine (25.0 grams; 0.085 mole). sodium cyanate(7.0 grams; 0.14 mole). 8.0 milliliters of methanol and 100 millilitersof acetonitrile was heated with agitation. at the boiling temperatureunder reflux conditions for a period of 3 days. Following the reactionperiod. the reaction mixture was filtered while hot to remove solidbyproducts. and the filtrate was cooled to about l0C. The yellowprecipitate formed upon cooling of the filtrate was removed byfiltration and recrystallized from a solution of hot carbontetrachloride. As a result of these operations. the desiredmethyl-2.3.5.6tetrachloro-4-pyridinecarbamate product was obtained as acrystalline solid melting a l8ll8l.5C. Elemental analysis calculated forC H CI N O (percent): C. 28.9; H. 1.38: C]. 48.9; N. one). Found(percentl: C. 2 ll. L43; Cl. 48.5; N. 9.82.

EXAMPLE 3 4Methylsulfonyl-2.3.5.otetrachloropyridine (5.0 grams; 0.017mole). potassium cyanate (2.0 grams; 0.03 mole). 20.0 milliliters ofacetonitrile and 2.0 milliliters of methanol were mixed in a glasspressure cell. The glass cell was placed in an oil bath and the reactionmixture was heated at a temperature of from about 100 to about 125C. fora period of l hour. Following the reaction period. the reaction mixturewas filtered while hot to remove solid byproducts and the filtrate wascooled to about minus 10C. The precipitate formed upon cooling of thefiltrate was filtered off and treated as in Example 2. The crystallinesolid was identified as methyl 2.3.5.ti-tetrachloropyridine carbamate.melting at l8l-l8l.5C.

EXAMPLE 4 A reaction mixture consisting of pentachloropyridine (20.0grams; 0.079 mole). sodium cyanate (20.0 grams; 0.4 mole) and 250milliliters of N- methylpyrrolidone were heated at a temperature ofabout [35 for a period of about 3 hours with agitation under thepressure of nitrogen. Following the reaction period. theN-methylpyrrolidone was removed from the reaction mixture bydistillation at 0.5 mm of pressure at a temperature of 80C. The reactionmixture was cooled and milliliters of ethanol. followed by 200milliliters of water. was added. The resultant suspen sion was extractedwith methylene chloride and dried; the solvent was removed from theextract by evaporation under reduced pressure. Chromatography of theresidue on silica gel gave 4amino-tetrachloropyridine. identical withauthentic samples, and ethyl 2.3.5.6- tetrachloropyridine carbamatemelting at ]78l 79C.

EXAMPLE 5 Pentachloropyridine (20.0 grams; 0.07 mole) was dissolved in250 milliliters of N-methylpyrrolidone containing sodium cyanate (20grams; 0.4 mole). The re sulting reaction mixture was heated at ll40C.in an atmosphere of nitrogen for a period of about 3 hours. Followingthe reaction period, the N- methylpyrrolidone was removed by vacuumdistillation over a period of about 2 hours. The dark brown residue thusobtained was treated with 200 milliliters of water and the resultantsuspension filtered to obtain a tan solid material which wascrystallized and recrystallized from a CHCl -hexane mixture. As a resultof these operations. the desired 4-amino-tetrachloropyridine com pound.identical with authentic samples. was obtained as a yellow crystallinesolid.

EXAMPLE 6 A reaction mixture consisting of 4-methylsulfonyl-2.3.5.6-tetrachloropyridine (25.0 grams; 0.085 mole). potassium cyanate(l0.3 grams; 0.l27 mole). and milliliters of acetonitrile was heatedwith agitation at the boiling temperature under reflux conditions for aperiod of about 20 hours. Following the reaction period. the reactionmixture was filtered While hot to remove a precipitate identified byinfrared analysis to be a mixture of unreacted potassium cyanate andisocyanurate product. The solvent was removed from the fil trate byevaporation under reduced pressure and the oily residue thus obtainedwas solidified by the addition of chloroform. The solid precipitateformed upon addition of chloroform was obtained by filtration andsuspended in ether. Subsequent acidification of the suspension withconcentrated hydrochloric acid gave a solid precipitate which wasfiltered off. The filtrate was evaporated in vacuo leaving a solidresidue which was recrystallized from refluxing acetonitrile. As aresult of these operations. the di-( 2.3.5.(1-tetrachloro-4- pyridine)isocyanurate product was recovered as a crystalline solid melting at338-339C What is claimed is:

l. A process for the preparation of a carbanilate compound whichcomprises reacting a phenyl compound. ring-substitutcd with at least onedisplaceable aprotic solvent is selected from the group consisting ofacetonitrile. dimethyl sulfoxide. dimethyl formamide. diglyme. monoglymeacetone. methyl ethyl ketone. dioxane. tetrahydrofuran andN-methylpyrrolidone.

3. The process ofclaim I wherein the alkali metal cy anatc is selectedfrom the group consisting of sodium. potassium. lithium. and cesium. andwherein the alkanol is selected from the group consisting of methanol.ethanol. propanol. isopropanol. and butanol.

4. The process ofclaim I wherein the high dielectricaprotic solvent isselected from the group consisting of acetonitrile andN-methylpyrrolidone. and wherein the alkali metal eyanate is selectedfrom the group consist ing of sodium and potassium.

5. The process ofclaim 1 wherein the reaction is carried out at atemperature of from about It) to about 200C.

6. The process ot'claim I wherein the reaction is car ried out at theboiling temperature of the reaction mi ture under reflux conditions.

7. The process of claim 1 wherein the ringsubstituted phenyl compound is3.4-dinitrochlorobenzene.

8. The process of claim 3 wherein ZA-dinitrochlorw benzene is reactedwith potassium cyan-ate in the pres ence of aeetonitrile and methanol.

1. A PROCESS FOR THE PREPARATION OF A CARBANILATE COMPOUND WHICHCOMPRISES REACTING A PHENYL COMPOUND, RINGSUBSTITUTED WITH AT LEAST ONEDISPLACEABLE SUBSTITUENT SELECTED FROM THE GROUP CONSISTING OF CHLORO,BROMO, FLUORO, IODO; -N2+-OSO2R, -SO2R, AND -SR2+, WHEREIN EACH RINDEPENDENTLY REPRESENTS HYDROGEN, PHENYL OR A LOWERALKYL RADICAL OFFORM ONE TO ABOUT 4 CARBON ATOMS, INCLUSIVE, WITH AN ALKALI METALCYANATE IN THE PRESENCE OF A HIGH DIELECTRIC-APROTIC SOLVENT AND ANALKANOL.
 2. The process of claim 1 wherein the high dielectric-aproticsolvent is selected from the group consisting of acetonitrile, dimethylsulfoxide, dimethyl formamide, diglyme, monoglyme acetone, methyl ethylketone, dioxane, tetrahydrofuran and N-methylpyrrolidone.
 3. The processof claim 1 wherein the alkali metal cyanate is selected from the groupconsisting of sodium, potassium, lithium, and cesium, and wherein thealkanol is selected from the group consisting of methanol, ethanol,propanol, isopropanol, and butanol.
 4. The process of claim 1 whereinthe high dielectric-aprotic solvent is selected from the groupconsisting of acetonitrile and N-methylpyrrolidone, and wherein thealkali metal cyanate is selected from the group consisting of sodium andpotassium.
 5. The process of claim 1 wherein the reaction is carried outat a temperature of from about 20 to about 200*C.
 6. The process ofclaim 1 wherein the reaction is carried out at the boiling temperatureof the reaction mixture under reflux conditions.
 7. The process of claim1 wherein the ring-substituted phenyl compound is2,4-dinitrochlorobenzene.
 8. The process of claim 3 wherein2,4-dinitrochlorobenzene is reacted with potassium cyanate in thepresence of acetonitrile and methanol.